MECHANISMS OF HYPERSENSITIVITY STATES

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The guinea pig is an excellent model in which to study mechanisms of immediate and delayed hypersensitivity. In our laboratory, we have preliminary evidence suggestive that we can make potentially important observations as to the role of homocytotropic antibody, mast cells, and basophils in guinea pig hypersensitivity states. Our data to date has demonstrated that both IgG1 and IgE can mediate polmonary contraction in the guinea pig and they seem to do so through separate tissue receptors. Furthermore, we have been able to isolate lung tissue mast cells and have the capability to study the biochemistry of these antibodies directly on this cell which has been shown to play an important role in immediate reactions. We also have the capability of isolating pure populations of blood basophilis (85-100% purity). Based upon these observations, we propose to study in detail the distinctive nature of the IgG1 and IgE pulmonary receptors. We plan to do this by suspending pulmonary tissue obtained from IgG1 or IgE sensitized animals in a superfusion chamber and simultaneously measure contraction and mediators released upon stimulation with specific antigen. We also would like to extend these tissue studies with homocytotropic antibody to the isolated pulmonary mast cell by studying this cell for IgG1 and IgE receptors and examining mediator release from these isolated cells when sensitized with IgG1 or IgE antibodies. A second separate but yet related part of our proposal is to examine the inflammatory provoking potential in guinea pig skin of isolated granules obtained from purified blood baseophils (90-100% purity). With this we hope to define some of the mechanisms of basophil involvement in delayed cutaneous reactions containing basophils. The similarity of the guinea pig to humans as far as primary mediators released by mast cells and basophils makes these studies of potential importance in understanding similar events in immediate and delayed hypersensitivity states in humans.